IHJ_Article_21.qxd 12/2/2006 5:53 PM Page 371 H ow To D o I t Transcoronary Ablation of Septal Hypertrophy (Tash) I Sathyamurthy Department of Cardiology, Apollo Hospitals, Chennai INTRODUCTION Until the early 1990s, surgical myectomy and dual-chamber pacing were considered treatments of choice for drug-resistant symptomatic hypertrophic obstructive cardiomyopathy (HOCM). In 1995, Ulrich Sigwart introduced a new technique—transcoronary ablation of septal hypertrophy (TASH)—at the Royal Brompton Hospital, London.1 The same year, Kuhn et al. performed the operation in Germany. 2 In India, cases of successful use of the technique were reported by Bahl et al.3 and Bhargava et al.4 Percutaneous transluminal septal myocardial ablation (PTSMA), which is another name for this technique, involves the injection of absolute alcohol into the target septal perforator branch of the left anterior descending (LAD) artery. This results in chemical necrosis, thereby producing a controlled myocardial infarction in the proximal interventricular septum. This, in turn, helps to achieve reduction of the basal septal thickness and ventricular septal remodeling , which result in the expansion of the left ventricular outflow tract (LVOT), and lessening of systolic anterior motion of the mitral leaflet and mitral regurgitation (MR). Indications 1. HOCM patients who have New York Heart Association (NYHA) Class III/IV symptoms despite optimal medical treatment with beta blockers (if contraindicated, calcium channel blockers) and disopyramide 2. A resting LVOT gradient of more than 30 mmHg 3. A post-ectopic gradient/post-exercise recovery gradient of more than 100 mmHg 4. Persistence of symptoms/recurrence of symptoms after surgical myectomy/DDD pacing 5. When surgical myectomy is contraindicated due to co-morbid conditions. Contraindications 1. Children/adolescents ⬍ 18 years 2. HOCM without resting or provocable outflow gradient 3. Patients with associated valvular or coronary artery disease 4. Associated MR of 3-plus or more MR due to mitral valve abnormalities or myxomatous degeneration of mitral valve 5. Mid-ventricular obstruction 6. Unsuitable septal anatomy Preparation and Consent The patient needs to be fasting for four hours before the procedure and all medications are stopped 48 hours before the procedure. Pre-procedure echocardiographic evaluation is done to confirm the diagnosis and to rule out fixed subaortic obstruction, mid-ventricular obstruction and associated intrinsic mitral valve disease resulting in MR. Informed consent is taken after explaining that there is a 1–2% risk of malignant ventricular arrhythmias and death, and a 10% risk of heart block, requiring the implantation of a pacemaker.5–7 PROCEDURE Right and left femoral arterial punctures and cannulations are carried out under local anesthesia, using 2% xylocaine. The right femoral vein is cannulated for temporary transvenous pacing. If programmed electrical stimulation to deliver PVCs is planned, the left femoral vein is also cannulated. Inj. heparin (100 U/kg) is administered intravenously. A routine coronary angiogram is performed to ascertain the septal anatomy (Figure 1). The left coronary artery is cannulated using a 6F/7F left coronary guiding catheter. A high torque floppy guide wire (0.014 inches) is introduced into the large first septal branch of the LAD or the target septal artery (TSA). A 1.5 mm/2 mm (rarely, 2.5 mm) overthe-wire balloon of a length of 12–15 mm is then positioned in the TSA and kept inflated at 4–6 atm. The guide wire is then retracted. Contrast is injected to check the position of the balloon, confirm that it is not protruding into the LAD artery, and ensure that it is tightly obliterating the septal branch. A temporary balloon occlusion of the TSA usually results in at least a 50% fall in the resting gradient and a Correspondence: Dr I Sathyamurthy, Interventional Cardiologist and Director, Department of Cardiology, Apollo Hospitals, 21 Greams Lane, Chennai – 600006 E-mail: ismurthy@md4.vsnl.net.in Indian Heart J 2006; 58: 371–374 371 IHJ_Article_21.qxd 12/2/2006 5:53 PM Page 372 Sathyamurthy 50 mmHg fall in the post-ectopic gradient. After the inflation of the balloon, 1–2 mL of nonionic contrast is injected through the central lumen (Figure 2). This helps to (a) check the position of the balloon in the desired septal branch; (b) ensure that there is no leakage of the contrast into the LAD artery; (c) check the rapid clearance of contrast, if any, into the venous system or the ventricular chambers (rapid washout of contrast is usually due to too many collaterals to the venous system, or due to fistulous communications to the left ventricle or right ventricle cavity); and (d) check the myocardial contrast opacification (tissue phase), to determine whether the TSA is perfusing any distant and unwanted areas of the myocardium or papillary muscles. After all these steps have been taken, the patient is sedated with intravenous morphine, pethidine or midazolam to alleviate pain. Then 2 mL of ethanol (95–98%) is taken in a 2 mL syringe. Of this, 1 mL is injected into the TSA initially. Figure 1. Left coronary angiogram: arrows showing large first septal perforator. Figure 2. Contrast injection through the lumen of the balloon catheter. Thick arrow shows balloon position. Thin arrows show contrast opacification of branches of first septal perforator/branch. Transthoracic echo transducer also seen. 372 Another 0.2mL of alcohol is injected after two minutes, and the procedure is repeated at two-minute intervals until the entire 2 mL of alcohol has been injected. Two minutes after this, 1 mL of saline is injected to wash out the alcohol. The balloon is deflated after five minutes and pulled back into the guiding catheter. A check coronary angiogram is performed to see whether the TSA is closed (Figure 3). It is not always necessary for the TSA to be totally occluded for a successful TASH.8 Ethanol-induced damage to the endothelial cells, interstitial cells, myocardium, and adrenergic and cholinergic nerve fibres is more significant than the complete occlusion of the TSA.8 If any resistance is encountered while injecting alcohol into the TSA, careful adjustment of the position of the balloon is necessary to relieve any sharp bend at the ostium of the TSA or at the tip of the guiding catheter. It is preferable to avoid forceful injection against resistance in order to avoid rupture. While adjusting the position of the balloon, it is important to ensure that it does not slip back into the LAD artery. Target Septal Artery The identification of the TSA is the key to the success of the TASH procedure. Usually it is a large first septal branch. The TSA should not be too small (supplying the inferior part of the proximal interventricular septum), or course too close to the LAD artery. The ideal views for identifying the TSA are right anterior oblique (RAO) 30o, left lateral 90o, and left anterior oblique (LAO) cranial or caudal views. Milking effect of the septal branch is not confirmatory of the TSA. If the TSA divides into two branches, it is preferable to inject alcohol into the basal side branch. In 90% of cases, the TSA arises from the LAD or diagonal artery. In the remaining 10% of cases, it may arise from the ramus, proximal circumflex, or posterolateral or posterior descending branches of the right coronary artery (RCA). The procedure is abandoned if (a) the septal arteries are thin, small and multiple (Figure 4); (b) there is difficulty passing the wire due to abnormal angulation of origin; (c) there is rapid Figure 3. Totally occluded first septal branch after alcohol ablation (arrow). Indian Heart J 2006; 58: 371–374 IHJ_Article_21.qxd 12/2/2006 5:53 PM Page 373 Transcoronary Ablation of Septal Hypertrophy (Tash) washout of contrast; or (d) there is no significant fall in gradient after temporary balloon occlusion. The first septal perforator (FSP) need not be the TSA in every case. The anatomy of the FSP artery is variable, in terms of size and distribution. An autopsy study by Singh et al.9 covering 10 patients confirmed that the FSP supplies areas other than the basal septum. This was also reported by our group.10 Echocardiography During Tash Intraprocedural myocardial contrast echocardiography during TASH is very useful in identifying the TSA. 11–13 Some operators prefer to use myocardial contrasts like Albunex, Levovist or Optiscan for this purpose. Our group, however, uses the routine nonionic angiographic contrasts like Omnipaque. Contrast by septal brightening helps one assess the septal opacification. Contrast should not brighten the right side of the septum, and rapid clearance of contrast into the ventricular chambers is undesirable. Echocardiography also helps measure the fall in gradient during TASH, as well as assess the degree of MR. It is preferable to combine the following techniques for the optimum result. 1. Functional anatomic approach when the culprit or TSA is exactly identified. 2. Super-selective approach of injecting contrast into branches of the first septal artery to opacify the basal septum. 3. Echo monitoring approach. Dose of Alcohol According to Kuhn et al., the maximum amount of alcohol to be injected should not exceed 2 mL in order to minimize the complications.7 Veselka et al. randomized 17 patients into two groups, one of which received a maximum of 2 mL and the other, 3.4 ⫾ 0.9 mL.14 There was no statistically significant difference in the clinical electrocardiograms (ECGs) and echocardiographic variables of the patients in the two groups, except that there was increased release of MB isoenzyme of creatine kinase (MBCK) in those who had received more than 2 mL of alcohol. Successful Ablation When the procedure is successful, an echocardiogram taken after six months shows a progressive decrease in the gradient. The septal thickness regresses and there is interventricular septal remodeling, with a resultant enlargement of the LVOT area.8,11,15–18 Biphasic Response There can be an acute response with a total abolition of the gradient due to stunned myocardium. This may be followed by the reappearance of 50% of the pre-procedural gradient after 48 hours. At six months’ follow-up, the gradient falls again. This is termed the ‘biphasic response’.19 Risk in Creatinine Phosphokinase (CPK) A twofold to tenfold rise in CPK can occur depending upon the amount of alcohol injected. This results in the production of a necrotic area equivalent to 3–10% of the left ventricular mass (approximately 20% of septal myocardium).6,18 COMPLICATIONS The mortality rate is 1–4%, and complete heart block requiring the implantation of a pacemaker has been reported in 10% of the cases. Premature ventricular contractions and non-sustained ventricular tachycardia are commonly noted. Right bundle branch block (RBBB) is encountered in 50–70% of cases after TASH. Certain rare complications, like acquired ventricular septal defect, stroke, massive myocardial infarction due to alcohol leakage into the LAD and left main coronary artery dissection related to the guiding catheter, have also been reported.11,15–18 AFTER PROCEDURE Figure 4. Left coronary angiogram showing multiple thin septal perforators not found suitable for TASH. Indian Heart J 2006; 58: 371–374 1. CPK and MBCPK must be assessed at 1 hour, 6 hours, 12 hours and 24 hours after TASH. 2. ECG monitoring and intravenous administration of heparin or low-molecular-weight heparin must be continued for seven days after the procedure. 3. An ECG and echocardiogram must be done soon after the procedure, after 24 hours, at discharge and 6 months’ follow-up. The echocardiogram is done to assess the LVOT gradient, severity of MR, intraventricular septal thickness and LVOT area. 4. The temporary pacemaker can be removed after 48–72 hours if there is no evidence of any high-grade atrioventricular block. 373 IHJ_Article_21.qxd 12/2/2006 5:53 PM Page 374 Sathyamurthy 5. If high-grade atrioventricular block persists beyond 72 hours, the patient needs implantation of a permanent pacemaker (preferably, a DDD pacemaker and VDD if there are economical constraints). 6. Discharge can be planned on the tenth day. Redo Tash If there is no reduction in the LVOT gradient after TASH, or if there is reappearance of more than 50% of the gradient at six months’ follow-up, the patient needs to undergo TASH again. In some cases, one may then need to choose septal branches of the posterior descending artery, or the posterior lateral branch, or septals not arising from the LAD or D1. 3. 4. 5. 6. 7. 8. CONCLUSION The TASH procedure is a promising non-surgical technique for the reduction of symptoms and the LVOT gradient in HOCM. Various workers have reported good clinical success rates with this technique, varying from 90–100%.15–19 The reduction in the LVOT gradient matched the clinical improvement, as well as the improvement in exercise capacity.20 The most frequent complication is the occurrence of RBBB in almost 50% of patients and high-grade atrioventricular block requiring permanent pacing in 10%. It has been shown that the use of intraprocedural myocardial contrast echocardiography and limiting the amount of alcohol to 2 mL can reduce the need for pacing to the minimum.11–14 The most dreaded complication is sudden in-hospital death, the incidence of which was about 3–4% in the above series. However, with advancement and modification of the technique and the experience gained by the operators, it has fallen to 1–2%. We reported our experience with 31 patients who underwent TASH and were followed up at two years.21 There was a reduction in the LVOT gradient in all but one patient (4%). There were two in-hospital deaths (6.4%). Total abolition of the gradient was noted in 9.7%, and more than 50% reduction in gradient in 71%. The peak systolic LVOT gradient decreased from a mean of 79 ⫾33 mmHg to 32 ⫾20 mmHg. The septal thickness decreased from 24 ⫾14 mm pre-procedure to 18 ⫾3 mm at follow-up. The TASH procedure requires expertise and experience which has a learning curve. Hypertrophic obstructive cardiomyopathy is an uncommon disease and a small number of patients are eligible for TASH. The procedure should not be regarded as a routine one and should be restricted to centers, and more particularly, to interventional cardiologists, with experience in TASH. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. REFERENCES 1. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211–14. 2. Kuhn H, Gietzen F, Leuner C, et al. 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